Pillay T S, Makgoba M W
Department of Chemical Pathology, Royal Postgraduate Medical School, Hammersmith Hospital, London.
S Afr Med J. 1991 May 18;79(10):607-13.
This review discusses recent advances in understanding of the structure and function of the insulin receptor and insulin action, and how these relate to the clinical aspects of insulin resistance associated with non-insulin-dependent diabetes and other disorders. Improved understanding of the molecular basis of insulin resistance could ultimately lead to a better understanding of the causation of these conditions and the design of rational therapy to ameliorate them. Here, particular attention is devoted to the initial events that follow the binding of insulin to its receptor, including changes in insulin receptor phosphorylation. Receptor-mediated insulin resistance may be a consequence of various factors including increased serine/threonine phosphorylation of the receptor with decreased tyrosine phosphorylation, receptor desensitization, auto-antibodies to the receptor and inherited structural defects in the insulin receptor. Defects in insulin action could also arise at post-receptor events particularly glucose transport. Other circulating hormones, such as the newly characterised islet amyloid polypeptide (amylin), may also cause insulin resistance.
本综述讨论了在胰岛素受体的结构与功能以及胰岛素作用的理解方面的最新进展，以及这些与非胰岛素依赖型糖尿病及其他病症相关的胰岛素抵抗的临床方面如何关联。对胰岛素抵抗分子基础的更深入理解最终可能会更好地理解这些病症的病因，并设计出合理的治疗方法来改善它们。在此，特别关注胰岛素与其受体结合后发生的初始事件，包括胰岛素受体磷酸化的变化。受体介导的胰岛素抵抗可能是多种因素的结果，包括受体丝氨酸/苏氨酸磷酸化增加而酪氨酸磷酸化减少、受体脱敏、针对受体的自身抗体以及胰岛素受体的遗传性结构缺陷。胰岛素作用的缺陷也可能出现在受体后事件中，尤其是葡萄糖转运方面。其他循环激素，如新发现的胰岛淀粉样多肽（胰淀素），也可能导致胰岛素抵抗。
